HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 25/25
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Hydralazine is a direct-acting arteriolar vasodilator that reduces peripheral resistance through relaxation of vascular smooth muscle, likely via nitric oxide-mediated increases in cGMP. Hydrochlorothiazide is a thiazide diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule, reducing sodium and water reabsorption and decreasing plasma volume.
| Metabolism | Hydralazine undergoes extensive hepatic metabolism via N-acetylation (polymorphic NAT2), also conjugated with glucuronic acid. Hydrochlorothiazide is not significantly metabolized; eliminated unchanged in urine. |
| Excretion | Hydralazine: 80% renal (as metabolites, 5-10% unchanged); Hydrochlorothiazide: 95% renal (as unchanged drug). |
| Half-life | Hydralazine: 2-8 hours (terminal half-life; prolonged in renal impairment; acetylator phenotype affects clearance); Hydrochlorothiazide: 6-15 hours (terminal half-life; increased in renal impairment). |
| Protein binding | Hydralazine: 87-90% bound to plasma proteins (primarily albumin); Hydrochlorothiazide: 40-68% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Hydralazine: 1.6 L/kg (large, indicating extensive tissue binding); Hydrochlorothiazide: 0.8 L/kg (distributes into extracellular fluid). |
| Bioavailability | Hydralazine: 30-50% (oral, due to first-pass metabolism; lower in fast acetylators); Hydrochlorothiazide: 65-75% (oral; food may increase absorption). |
| Onset of Action | Hydralazine: 10-20 minutes (oral, with peak effect at 30-120 minutes); Hydrochlorothiazide: 2 hours (oral, with peak effect at 4-6 hours). |
| Duration of Action | Hydralazine: 6-8 hours (antihypertensive effect; acetylator phenotype influences duration); Hydrochlorothiazide: 12-16 hours (diuretic and antihypertensive effects). |
One tablet orally twice daily, titrated based on blood pressure response; maximum dose: one tablet four times daily.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 30-50 mL/min: one tablet once daily. GFR <30 mL/min: not recommended due to thiazide component. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: initial dose reduced by 50%. Child-Pugh Class C: contraindicated. |
| Pediatric use | 0.75-1.0 mg/kg/day hydralazine component divided every 6-12 hours; maximum 7.5 mg/kg/day. Hydrochlorothiazide 0.5-1.0 mg/kg/dose every 12-24 hours; maximum 2.5 mg/kg/day. Use caution in neonates. |
| Geriatric use | Initiate at one-half tablet orally once daily; titrate slowly due to increased risk of hypotension, hypokalemia, and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Breastfeeding | Hydralazine: Present in breast milk; infant dose <1% maternal weight-adjusted dose; M/P ratio not reported. Hydrochlorothiazide: Present in breast milk; M/P ratio 0.5-1.0; may suppress lactation at high doses. Use with caution, monitor infant for electrolyte imbalances. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | edema |
| Serious Effects |
["Hypersensitivity to hydralazine, hydrochlorothiazide, or sulfonamide-derived drugs.","Anuria (hydrochlorothiazide).","Acute myocardial infarction (hydralazine).","Dissecting aortic aneurysm (hydralazine).","Severe tachycardia or high-output heart failure (hydralazine).","Rheumatic mitral valve disease (hydralazine)."]
| Precautions | ["May cause a lupus-like syndrome (especially with hydralazine) - monitor for symptoms (fever, arthralgia, serositis); discontinue if positive ANA or lupus-like reaction.","Hydralazine may cause tachycardia, angina, or myocardial infarction in susceptible patients; use caution in coronary artery disease.","Hydrochlorothiazide may cause electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia), volume depletion, and acute angle-closure glaucoma.","Can precipitate gout due to increased serum uric acid.","May increase blood glucose, cholesterol, and triglycerides.","Use caution with impaired renal or hepatic function."] |
Loading safety data…
| Hydralazine: Risk in first trimester uncertain; associated with maternal hypotension and potential fetal hypoxia in second/third trimester. Hydrochlorothiazide: Avoid in first trimester (oligohydramnios, fetal electrolyte disturbances); second/third trimester risk of fetal/neonatal jaundice, thrombocytopenia, electrolyte abnormalities. Both: Fetal bradycardia, hypovolemia, and metabolic effects possible. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, serum electrolytes, renal function, lupus serology (ANA). Fetal: Growth ultrasound, amniotic fluid index, heart rate monitoring. Neonatal: Platelet count, bilirubin, electrolytes. |
| Fertility Effects | Hydralazine: No reported direct fertility effects. Hydrochlorothiazide: May cause mild glucose intolerance; no direct impact on fertility. Combined: Limited data, but no major impairment expected. |